In vitro islet exposure to interleukin 1 beta inhibits the beta-cell response to glucose. We have studied whether a similar inhibition also occurs in response to the sulphonylurea glyburide. Rat pancreatic islets were cultured for 24 h in the presence or absence of 50 U/ml interleukin 1 beta and then stimulated with either glucose or glyburide for 1 h at 37 degrees C. In control islets basal insulin secretion was 117 +/- 32 pg.islet-1.h-1 (mean +/- SEM, n = 7) and greatly increased in response to 16.7 mmol/l glucose (2140 +/- 293) or 10 mumol/l glyburide (1464 +/- 234). When islets were pre-exposed to interleukin 1 beta, insulin release was significantly reduced in response to glucose (323 +/- 80, p < 0.001) but not in response to glyburide (1316 +/- 185). Since both glucose and glyburide influence beta-cell K+ and Ca2+ efflux, to further investigate this different response in islets exposed to interleukin 1 beta we measured both Rb+ efflux (as index of the ATP-sensitive K+ channel activity) and Ca2+ uptake. In control islets, the increased insulin secretion in response to 16.7 mmol/l glucose or 10 mumol/l glyburide was associated with a reduction of 86Rb efflux (decrement of -50 +/- 1.2% and -49 +/- 2.3%, respectively, mean +/- SEM, n = 5). In contrast, in interleukin 1 beta pre-exposed islets both glucose and glyburide stimulation only slightly modified 86Rb efflux (decrement of -19 +/- 1.9% and -5.3 +/- 3.1%, respectively, n = 5, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)